Abstract 4409
Background
Worldwide, Breast cancer (BC) is the leading cause of cancer-related mortality in women. In Argentina, breast cancer is the second leading cause of death in women, with an incidence of 18.47%. Given the importance of breast cancer for public health, and the diversity of patients’ response to current therapies, the identification of new therapeutic targets is crucial. Rac1 is a Rho GTPase widely involved in motility, mitogenesis, transformation, and metastasis. P-Rex1 is a Rac1 activator essential for the migration of breast cancer cells. It has been reported that P-Rex1 is overexpressed in breast cancer of the luminal type and that its silencing inhibits the migration of cancer cells. In order to validate P-Rex1 as a therapeutic target and/or prognostic biomarker, we aimed to analyze its presence in samples of Argentinean patients from the Marie Curie Hospital of Buenos Aires City, and determine its relationship with clinical and histopathological parameters.
Methods
The levels of P-Rex1 were determined both in biopsy material and in tumor tissue (and its corresponding healthy adjacent tissue) from primary surgery of patients not undergoing neoadjuvant therapy. The levels of messenger RNA (mRNA) were analyzed by quantitative PCR and protein by western blot (WB) and immunohistochemistry.
Results
When the mRNA levels of the biopsies classified according to the molecular subtype were compared, elevated P-Rex1 levels were observed not only in those samples classified as ER+/PR+ breast cancer but also in 50% of the samples of triple negative breast cancer (TNBC). These data were validated by an in-silico analysis made from public access databases (Metabric and the GEO repository of NCBI). P-Rex overexpression in TNBC patients has not been previously reported. The aberrant expression of P-Rex1 was detected in all stages of the disease, and a negative correlation between the expression of P-REX1 and the proliferation marker Ki-67 was determined. P-Rex1 levels were significantly higher in tumors compared to normal breast samples, in agreement with previous reports.
Conclusions
These results confirm the potential of P-Rex1 as a therapeutic target not only for the treatment of luminal tumors but also for a certain population of TNBC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Eva Wertheimer.
Funding
Instituto Nacional del Cáncer-Ministerio de Salud-Argentina (INC, Asistencia Financiera IV, 2018).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract
4325 - Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: insights of the MATCH-R study
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract